The contribution of ultrasound-aided particle size reduction to the efficiency of the subsequent enzymatic hydrolysis and the accompanying morphological changes of bleached cotton and linen powders were investigated. The aqueous suspensions of cellulosic powders were pretreated either with an ultrasonic bath (US-B) or with a horn-type reactor (US-H). Results revealed that the impact of US-H was more pronounced than that of the US-B. Clearly, the linen particles were more sensitive to ultrasonication than cotton. The US-H modified the particle size distribution differently for the cotton and linen powders and reduced the mean size of particles from 49 to 40 µm and from 123 to 63 µm, respectively. A significant increase in the water retention and water sorption capacity was also measured. The smaller particles with increased accessibility were preferably digested in the enzyme treatment, resulting in a considerably higher concentration of reducing sugars and an enrichment of the residual particles with a larger average size (cotton: 47 µm; linen: 66 µm).